Intervertebral nucleus and annulus implants and methods of use thereof

ABSTRACT

The invention encompasses devices and methods for treating one or more damaged, diseased, or traumatized intervertebral discs to reduce or eliminate associated back pain. Specifically, the invention encompasses intervertebral nucleus and annulus implants that are resistant to migration in and/or expulsion from an intervertebral disc space. The invention further encompasses kits including the implantable devices of the invention and associated delivery tools to treat annular and nuclear tissue.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 12/725,988, filed Mar. 17, 2010, and entitled “IntervertebralNucleus and Annulus Implants and Method of Use Thereof.” The entireapplication is hereby incorporated by reference in its entirety.

FIELD OF THE INVENTION

The invention encompasses devices and methods for treating one or moredamaged, diseased, or traumatized intervertebral discs to reduce oreliminate associated back pain. Specifically, the invention encompassesintervertebral nucleus pulposus and annulus fibrosus implants that areresistant to migration in and/or expulsion from an intervertebral discspace. The invention further encompasses kits including the implantabledevices of the invention and associated delivery tools to treat annularand nuclear tissue.

BACKGROUND OF THE INVENTION

The spinal column is formed from a number of bony vertebrae, which intheir normal state are separated from each other by intervertebraldiscs. Intervertebral discs provide mobility and a cushion between thevertebrae. These discs are comprised of the annulus fibrosus and thenucleus pulposus both of which are soft tissue. At the center of thedisc is the nucleus pulposus. The nucleus pulposus is surrounded by theannulus fibrosus, which is comprised of cells (fibrocyte-like andchondrocyte-like), collagen fibers, and non-fibrillar extracellularmatrix. The intervertebral disc acts in the spine as a stabilizer and asa mechanism for force distribution between adjacent vertebral bodies.Without a competent disc, collapse of the intervertebral disc may occurcontributing to abnormal joint mechanics and premature development ofdegenerative and/or arthritic changes.

The normal intervertebral disc has an outer ligamentous ring called theannulus surrounding the nucleus pulposus. The annulus binds the adjacentvertebrae together and is constituted of collagen fibers that areattached to the vertebrae and cross each other so that half of theindividual fibers will tighten as the vertebrae are rotated in eitherdirection, thus resisting twisting or torsional motion. The nucleuspulposus is constituted of soft tissue, having about 85% water content,which moves about during bending from front to back and from side toside.

The aging process contributes to gradual changes in the intervertebraldiscs. The annulus loses much of its flexibility and resilience,becoming more dense and solid in composition. The aging annulus may alsobe marked by the appearance or propagation of cracks or fissures in theannular wall. Similarly, the nucleus desiccates increasing viscosity andthus losing its fluidity. In combination, these features of the agedintervertebral discs result in less dynamic stress distribution becauseof the more viscous nucleus pulposus, and less ability to withstandlocalized stresses by the annulus fibrosus due to its desiccation, lossof flexibility and the presence of fissures. Fissures can also occur dueto disease or other pathological conditions. Occasionally fissures mayform rents through the annular wall. In these instances, the nucleuspulposus is urged outwardly from the subannular space through a rent,often into the spinal column. Extruded nucleus pulposus can and oftendoes mechanically press on the spinal cord or spinal nerve rootlet. Thispainful condition is clinically referred to as a ruptured or herniateddisc.

In the event of annulus rupture, the subannular nucleus pulposusmigrates along the path of least resistance forcing the fissure to openfurther, allowing migration of the nucleus pulposus through the wall ofthe disc, with resultant nerve compression and leakage of chemicals ofinflammation into the space around the adjacent nerve roots supplyingthe extremities, bladder, bowel and genitalia. The usual effect of nervecompression and inflammation is intolerable back or neck pain, radiatinginto the extremities, with accompanying numbness, weakness, and in latestages, paralysis and muscle atrophy, and/or bladder and bowelincontinence. Additionally, injury, disease or other degenerativedisorders may cause one or more of the intervertebral discs to shrink,collapse, deteriorate, or become displaced, herniated, or otherwisedamaged and compromised. There are a number of suspected causes of discrelated pain, and in any given patient, one or more of these causes maybe present.

The inventors have developed compositions for the treatment of discrelated disorders, particularly in the treatment of disc related painassociated with a damaged or otherwise unhealthy disc.

SUMMARY OF THE INVENTION

The inventors have surprisingly found that the compositions and methodsof the invention for annulus fibrosus and nucleus pulposus replacementand repair overcome the shortcomings associated with currently usedreplacement and repair technology.

Accordingly, in one embodiment, the invention encompasses a nucleuspulposus replacement composition comprising an elastomeric or polymericmaterial comprising a central cavity; a plurality of elastomeric beads;and a biocompatible fluid or gel. In certain exemplary embodiments, thenucleus pulposus replacement composition is in the form of a balloon,and the plurality of elastomeric beads is suspended in the biocompatiblefluid or gel and fills a central cavity of the nucleus pulposusreplacement composition. In other exemplary embodiments, the balloon isfinable in situ to conform to the dimensions of an intevertebral discspace and to an inner wall of an annulus fibrosus.

In another embodiment, the invention encompasses a nucleus pulposusreplacement composition comprising one or more biocompatible polymericor elastomeric materials in the form of a pre-shaped balloon. In certainembodiments, the nucleus pulposus replacement composition includes acentral cavity and one or more envelope cavities surrounding the centralcavity. In certain embodiments, the biocompatible polymeric orelastomeric material comprises a solid, deformable, and load-bearingmaterial.

In another embodiment, the invention encompasses a nucleus pulposusreplacement composition comprising one or more biocompatible polymericor elastomeric materials in the form of a plurality of concentric coilsthat are conically shaped, wherein the outermost perimeter of theplurality of concentric coils is capable of conforming to an inner wallof an annulus fibrosus. In certain embodiments, the nucleus replacementcomposition is comprised of a biocompatible polymeric or elastomericmaterial coiled into a plurality of concentric coils of narrowingdiameter (e.g., conically shaped), which are deformable andload-bearing.

In another embodiment, the invention encompasses a nucleus pulposusreplacement composition comprised of one or more biocompatible polymericor elastomeric materials in the shape of a plurality of string-likeimplants. In certain embodiments, the nucleus pulposus replacementcomposition is comprised of a plurality of string-like implantscomprised of elastomeric microbeads that form a cylindrical string,which are deformable and load-bearing.

In another embodiment, the invention encompasses a nucleus pulposuscontainment shell comprising:

a. an outer shell comprised of a biocompatible material;

b. an inner surface capable of being filled with a load bearingpolymeric or elastomeric material,

c. a unidirectional valve to allow filling of the inner surface; and

d. a sealing crimp to prevent leakage of the load bearing polymeric orelastomeric material filling the inner surface.

wherein the outer shell has an cylindrical-like or ellipsoid-like shapeand wherein a top surface and/or a bottom surface of the outer shell aretextured to provide anchorage with one or more vertebral endplates.

In another embodiment, the invention encompasses a nucleus pulposuscontainment shell comprising:

a. an outer shell comprised of a biocompatible material;

b. an inner surface capable of being filled with a load bearingpolymeric or elastomeric material,

c. a unidirectional valve to allow filling of the inner surface; and

d. a sealing crimp to prevent leakage of the load bearing polymeric orelastomeric material filling the inner surface.

wherein the outer shell has an tubular ring-like shape (i.e.,donut-shaped including a central orifice), wherein a top surface and/ora bottom surface of the outer shell are textured to provide anchoragewith one or more vertebral endplates.

In another embodiment, the invention encompasses a combination nucleuspulposus replacement and annulus fibrosus repair system comprising:

a. nucleus replacement composition comprising:

-   -   i. an outer surface comprised of a biocompatible material and        adapted to conform to an inner wall of an annulus fibrosus and        comprising a valve attached to the outer surface comprising a        rigid socket geometry; and    -   ii. an inner surface having a central recess capable of        receiving a load bearing polymeric or elastomeric material,

wherein the outer and inner surfaces define a solid, deformablethickness therebetween; and

b. an annulus fibrosus plug comprising a ball-fitting that connects withthe valve of the nucleus replacement composition, wherein the ballfitting comprises a plug of a natural or synthetic material thatpromotes cell in-growth with the surrounding annulus fibrosus.

In another embodiment, the invention encompasses a method of replacing anucleus pulposus and repairing an annulus fibrosus comprising:

a. removing the nucleus pulposus through an opening in the annulusfibrosus to create a nucleus cavity;

b. inserting a nucleus pulposus replacement composition comprising afillable central cavity into the nucleus cavity;

c. filling a plurality of elastomeric beads suspended in a biocompatiblefluid or gel into the nucleus pulposus replacement composition; and

d. plugging the annulus fibrosus.

BRIEF DESCRIPTION OF THE FIGURES

A more complete understanding of the present invention may be obtainedby reference to the accompanying drawings, when considered inconjunction with the subsequent detailed description. The embodimentsillustrated in the drawings are intended only to exemplify the inventionand should not be construed as limiting the invention to the illustratedembodiments, in which:

FIG. 1a illustrates a non-limiting, exemplary schematic of the insertionof a deflated single- or multi-lumen biocompatible polymeric orelastomeric balloon into the nucleus pulposus cavity using a catheter orendoscope. FIG. 1b illustrates the inflating of the balloon usingmechanical or hydraulic means with load bearing microbeads suspended inbiocompatible fluid or gel. FIG. 1c illustrates the plugging of theannular injury using a catheter or endoscope.

FIG. 2a illustrates a non-limiting, exemplary blown up view of theinsertion of a deflated single- or multi-lumen balloon 110 into thenucleus pulposus cavity 105 using a catheter or endoscope 130, which isinserted through an injury or tear in the annulus fibrosus 120. FIG. 2billustrates the inflating of the balloon using mechanical or hydraulicmeans with load bearing microbeads 140 suspended in biocompatible fluidor gel. FIG. 2c illustrates the plugging of the annular injury 160 andremoval of the catheter or endoscope.

FIG. 3a illustrates a non-limiting, exemplary spring nucleus replacementcomprised of one or more biocompatible polymeric or elastomericmaterials in the form of a plurality of concentric coils 301 that areconically shaped. A top view in FIG. 3b illustrates a non-limiting,exemplary embodiment, wherein the concentric circles that are compressedleaving no space or very little space between the coils.

FIG. 4a illustrates a non-limiting, exemplary pre-shaped balloon nucleusreplacement composition 401 that can be created to conform to theintervertebral disc levels (e.g., L1-S1). In certain illustrativeembodiments, the shape and height can be cut by a surgeon to conform theintervertebral disc height. In certain non-limiting, exemplaryembodiments, FIG. 4b illustrates a single envelope system, which allowsfilling the envelope cavity space 410, the center cavity 420, or both ofthem.

FIG. 5a illustrates a non-limiting, exemplary thin string nucleusimplant composition 501. The thin string can be implanted through a tearor fissure in the annulus fibrosus and in illustrative embodiments thestring is larger than the tear or fissures to prevent leakage. FIG. 5billustrates a blown up view of a thin string 510.

FIGS. 6a and 6b illustrate a non-limiting, exemplary nucleus pulposuscontainment shell including an outer shell having a cylindrical orellipsoid-like shape (i.e., having a curved diameter 601 and flattenedtop and/or bottom surface 610). In certain embodiments, the nucleuspulposus containment shell includes a textured top and/or bottom surface620 to provide anchorage with vertebral endplates and an optionallytextured surface along the curved perimeter. The implant can be filledwith a load bearing polymeric or elastomeric material filling to allowthe implant to conform to the shape of the annulus fibrosus 6 b. In anillustrative, non-limiting embodiment, the implant is comprised of ametal foil shell or polymer shell (e.g., urethanes, silicones), or acombination thereof, a unidirectional valve 630 for filling the innersurface; and a sealing crimp 640 to prevent leakage of the load bearingpolymeric or elastomeric material filling the inner surface.

FIGS. 7a-7c illustrate a non-limiting, exemplary nucleus pulposuscontainment shell including an outer shell having a tubular ring-likeshape and a textured top and bottom surface to provide anchorage withvertebral endplates and an optionally textured surface along the curvedperimeter. The implant can be filled with a load bearing polymeric orelastomeric material filling to allow the implant to conform to theshape of the annulus fibrosus. In an illustrative, non-limitingembodiment, the implant includes a metal foil shell or polymer shell(e.g., urethanes, silicones), or a combination thereof, a unidirectionalvalve for filling the inner surface; a unidirectional valve 720 forfilling the inner surface; and a sealing crimp 730 to prevent leakage ofthe load bearing polymeric or elastomeric material filling the innersurface.

FIG. 8 illustrates a non-limiting, exemplary annulus fibrosus includingan opening wherein the nucleus pulposus has been removed to create acavity in the annulus fibrosus. Through the opening a nucleus pulposusreplacement composition of the invention can be inserted into theannulus fibrosus.

FIG. 9a illustrates a non-limiting, exemplary nucleus pulposus implant901 comprised of a biocompatible polymeric or elastomeric material andincluding a valve that allows the implant to be filled, for example,with a load bearing polymeric or elastomeric material after insertioninto the annulus fibrosus cavity. The valve can include a rigid socketgeometry 910 for connecting with an annulus fibrosus plug that includesa ball fitting that connects with the valve of the nucleus implant. FIG.9b illustrates a non-limiting, exemplary example of the nucleus pulposusimplant inserted into the cavity of the annulus fibrosus.

FIG. 10a illustrates a non-limiting, exemplary annulus fibrosus plugincluding a weave of fibers 1001 or a sponge 1010 (i.e., a natural orsynthetic material) to make a porous plug that is permanently attachedto the prongs on the plug. The porous plug promotes in vivo cellin-growth from the surrounding annulus. FIG. 10b illustrates anon-limiting, exemplary annulus fibrosus plug that is preformed withdifferent plug geometries that allow a surgeon to cut the plug fromstock size plugs to suit a particular annulus fibrosus defect size.

FIG. 11 illustrates a non-limiting, exemplary schematic of a nucleuspulposus implant including a check valve that can be attached an annulusfibrosus plug. The annulus fibrosus plug is connected to the nucleuspulposus valve using a guide that is connected to the annulus fibrosusplug. After attaching the annulus fibrosus plug to the nucleus pulposusimplant the guide can be removed by mechanical (e.g., by unscrewing) orhydraulic means.

FIG. 12a illustrates a non-limiting, exemplary embodiment of a nucleuspulposus implant including a check valve just prior to attachment ofannulus fibrosus plug. The annulus fibrosus plug is attached to a guideand is inserted into the annulus fibrosus tear or fissure. FIG. 12billustrates a non-limiting, exemplary embodiment of a nucleus pulposusimplant including a check valve and the attachment of annulus fibrosusplug. The annulus fibrosus plug is attached to a guide and beinginserted into the annulus fibrosus tear, to engage with the socket ofthe check valve.

DETAILED DESCRIPTION OF THE INVENTION

The invention generally encompasses nucleus pulposus and annulusfibrosus replacement and repair technology.

In one embodiment, the invention encompasses a nucleus pulposusreplacement composition comprising one or more elastomeric or polymericmaterials comprising a central fillable cavity; a plurality ofelastomeric beads; and a biocompatible fluid or gel, wherein theplurality of elastomeric beads are suspended in the biocompatible fluidor gel and each fill the central cavity of the nucleus pulposusreplacement composition.

In certain illustrative embodiments, the nucleus pulposus replacementcomposition is in the form of a balloon.

In certain illustrative embodiments, the central fillable cavity isfilled in situ to conform to the dimensions of an intevertebral discspace and to an inner wall of an annulus fibrosus.

In certain illustrative embodiments, the central fillable cavity ispre-shaped with dimensions that conform to an intevertebral disc spacecorresponding to an inner wall of an annulus fibrosus such that uponfilling the central cavity the nucleus pulposus replacement compositionwill conform to the walls of the annulus fibrosus.

In certain illustrative embodiments, the central fillable cavitycomprises a single lumen.

In certain illustrative embodiments, the central fillable cavitycomprises more than one lumen.

In certain illustrative embodiments, the central fillable cavitycomprises a central cavity and one or more envelope cavities surroundingthe central cavity.

In certain illustrative embodiments, the one or more biocompatiblepolymers or elastomers comprise thermoplastic polyurethane elastomer,polysiloxane modified styrene-ethylene/butylene block copolymer,polycarbonate-urethane, polycarbonate-urethane cross-linked by a polyol,silicone rubber, silicone elastomer, polyether urethane, polyesterurethane, a polyether polyester copolymer, polypropylene oxide, styreneisoprene butadiene, and combinations thereof.

In certain illustrative embodiments, the central cavity and one or moreenvelope cavities surrounding the center cavity can be independentlyfilled with a plurality of elastomeric beads and the biocompatible fluidor gel. In certain embodiments, the plurality of elastomeric beads issuspended in the biocompatible fluid.

In certain illustrative embodiments, the elastomeric beads are comprisedof silicone, urethane, silicone-urethane copolymer,polycarbonate-urethane copolymer, polyethylene terephthalate, orcombinations thereof.

In certain illustrative embodiments, the biocompatible fluid or gel issaline, beta-glucan, hyaluronic acid and derivatives thereof, polyvinylpyrrolidone or a hydrogel derivative thereof, dextrans or a hydrogelderivative thereof, glycerol, polyethylene glycol, Pluronic® type blockcopolymers (i.e., based on ethylene oxide and propylene oxide),polyvinyl acetate, succinylated collagen, liquid collagen, and otherpolysaccharides or biocompatible polymers or combinations thereof.

In certain illustrative embodiments, the composition is porous.

In certain illustrative embodiments, the porous composition furthercomprises one or more bioactive agents, which diffuse into thesurrounding tissue after implantation.

In certain illustrative embodiments, the one or more bioactive agentspromote growth or reduce inflammation.

In another embodiment, the invention encompasses a nucleus pulposusreplacement composition comprising one or more biocompatible polymericor elastomeric materials in the form of a pre-shaped balloon, whereinthe biocompatible elastomeric or polymeric material comprises a centralcavity and one or more envelope cavities surrounding the center cavity.

In certain illustrative embodiments, one or more biocompatible polymericor elastomeric material comprises thermoplastic polyurethane elastomer,polysiloxane modified styrene-ethylene/butylene block copolymer,polycarbonate-urethane, polycarbonate-urethane cross-linked by a polyol,silicone rubber, silicone elastomer, polyether urethane, polyesterurethane, a polyether polyester copolymer, polypropylene oxide, andcombinations thereof.

In certain illustrative embodiments, the center cavity and one or moreenvelope cavities surrounding the center cavity can be independentlyfilled with a plurality of elastomeric beads and/or a biocompatiblefluid or gel.

In certain illustrative embodiments, the elastomeric beads are comprisedof silicone, urethane, silicone-urethane copolymer,polycarbonate-urethane copolymer, polyethylene terephthalate, orcombinations thereof.

In certain illustrative embodiments, the biocompatible fluid or gel iscomprised of saline, beta-glucan, hyaluronic acid and derivativesthereof, polyvinyl pyrrolidone or a hydrogel derivative thereof,dextrans or a hydrogel derivative thereof, glycerol, polyethyleneglycol, Pluronic® type block copolymers (i.e., based on ethylene oxideand propylene oxide), succinylated collagen, liquid collagen, and otherpolysaccharides or biocompatible polymers or combinations thereof.

In certain illustrative embodiments, the composition is porous. Incertain illustrative embodiments, the porous composition furthercomprises one or more bioactive agents, which diffuse into thesurrounding tissue after implantation.

In certain illustrative embodiments, one or more bioactive agentspromote growth or reduce inflammation.

In another embodiment, the invention encompasses a nucleus pulposusreplacement composition comprising one or more biocompatible polymericor elastomeric materials conically shaped in the form of a plurality ofconcentric coils of narrowing diameter, wherein the outermost perimeterconforms to an inner wall of an annulus fibrosus.

In certain illustrative embodiments, the one or more biocompatiblepolymeric or elastomeric material comprises thermoplastic polyurethaneelastomer, polysiloxane modified styrene-ethylene/butylene blockcopolymer, polycarbonate-urethane, polycarbonate-urethane cross-linkedby a polyol, silicone rubber, silicone elastomer, polyether urethane,polyester urethane, a polyether polyester copolymer, polypropyleneoxide, and combinations thereof.

In certain illustrative embodiments, the composition has a height thatconforms with a vertebral disc height.

In certain illustrative embodiments, the composition is porous.

In certain illustrative embodiments, the porous composition furthercomprises one or more bioactive agents, which diffuse into thesurrounding tissue after implantation.

In certain illustrative embodiments, the one or more bioactive agentspromote growth or reduce inflammation.

In another embodiment, the invention encompasses a nucleus replacementcomposition comprised of one or more biocompatible elastomeric orpolymeric materials in the shape of a plurality of string-like implants.

In certain illustrative embodiments, the string-like implants are formedfrom a plurality of microbeads that form a cylindrical string.

In certain illustrative embodiments, the one or more biocompatibleelastomeric or polymeric materials comprise thermoplastic polyurethaneelastomer, polysiloxane modified styrene-ethylene/butylene blockcopolymer, polycarbonate-urethane, polycarbonate-urethane cross-linkedby a polyol, silicone rubber, silicone elastomer, polyether urethane,polyester urethane, a polyether polyester copolymer, polypropyleneoxide, and combinations thereof.

In certain illustrative embodiments, the microbeads are comprised ofsilicone, urethane, silicone-urethane copolymer, polycarbonate-urethanecopolymer, polyethylene terephthalate, or combinations thereof.

In certain illustrative embodiments, the composition is porous.

In certain illustrative embodiments, the porous composition furthercomprises one or more bioactive agents, which diffuse into thesurrounding tissue after implantation.

In certain illustrative embodiments, the one or more bioactive agentspromote growth or reduce inflammation.

In another embodiment, the invention encompasses a nucleus pulposuscontainment shell comprising:

a. an outer shell comprised of a biocompatible material;

b. an inner surface capable of receiving a load bearing polymeric orelastomeric material,

c. a unidirectional valve to allow filling of the inner surface; and

d. a sealing crimp to prevent leakage of the load bearing polymeric orelastomeric material filling the inner surface.

wherein the outer shell has an cylindrical-like shape,

wherein a top surface and/or a bottom surface of the outer shell aretextured to provide anchorage with one or more vertebral endplates.

In certain illustrative embodiments, the outer shell is comprised of ametallic foil-like material comprised NiTi alloy, stainless steel,titanium or combinations thereof.

In certain illustrative embodiments, the outer shell is comprised of apolymeric material, a biodegradable or bioresorbable material, or acombination thereof.

In certain illustrative embodiments, the polymeric material ispolypropylene, polyethylene, polyurethane, polycarbonate urethane,Polyetheretherketone (PEEK), polyester, PET, poly olefin copolymer,polypropylene, polyethylene or a combination thereof.

In certain illustrative embodiments, the biodegradable or bioresorbablematerial is collagen, cellulose, polysaccharide, polyglycolic acid(PGA), a polylevolactic acid (PPLA), a polydioxanone (PDA), polylacticacid (PDLLA) or a combination thereof.

In certain illustrative embodiments, the load bearing polymeric orelastomeric material is thermoplastic polyurethane elastomer,polysiloxane modified styrene-ethylene/butylene block copolymer,polycarbonate-urethane, polycarbonate-urethane cross-linked by a polyol,silicone rubber, silicone elastomer, polyether urethane, polyesterurethane, a polyether polyester copolymer, polypropylene oxide,silicone, urethane, silicone-urethane copolymer, polycarbonate-urethanecopolymer, polyethylene terephthalate, saline, beta-glucan, hyaluronicacid and derivatives thereof, polyvinyl pyrrolidone or a hydrogelderivative thereof, dextrans or a hydrogel derivative thereof, glycerol,polyethylene glycol, succinylated collagen, liquid collagen, and otherpolysaccharides or biocompatible polymers or combinations thereof.

In certain illustrative embodiments, the composition is porous.

In certain illustrative embodiments, the porous composition furthercomprises one or more bioactive agents, which slowly diffuse into thesurrounding tissue after implantation.

In certain illustrative embodiments, the one or more bioactive agentspromote growth or reduce inflammation.

In another embodiment, the invention encompasses a nucleus pulposuscontainment shell comprising:

a. an outer shell comprised of a biocompatible material;

b. an inner surface capable of receiving a load bearing polymeric orelastomeric material,

c. a unidirectional valve for filling the inner surface; and

d. a sealing crimp to prevent leakage of the load bearing polymeric orelastomeric material filling the inner surface.

wherein the outer shell has an tubular ring-like shape, wherein a topsurface and/or a bottom surface of the outer shell are textured toprovide anchorage with vertebral endplates.

In certain illustrative embodiments, the outer shell is comprised of ametallic foil-like material comprised NiTi alloy, stainless steel,titanium or combinations thereof.

In certain illustrative embodiments, the outer shell is comprised of apolymeric material, a biodegradable or bioresorbable material, or acombination thereof.

In certain illustrative embodiments, the polymeric material ispolypropylene, polyethylene, polyurethane, polycarbonate urethane,Polyetheretherketone (PEEK), polyester, PET, poly olefin copolymer,polypropylene, polyethylene or a combination thereof.

In certain illustrative embodiments, the biodegradable or bioresorbablematerial is collagen, cellulose, polysaccharide, polylactic acid (PLA),polyglycolic acid (PGA), polylactic acid/polyglycolic acid, apolylevolactic acid (PPLA), a polydioxanone (PDA), polylactic acid(PDLLA) or a combination thereof.

In certain illustrative embodiments, the load bearing polymeric orelastomeric material is thermoplastic polyurethane elastomer,polysiloxane modified styrene-ethylene/butylene block copolymer,polycarbonate-urethane, polycarbonate-urethane cross-linked by a polyol,silicone rubber, silicone elastomer, polyether urethane, polyesterurethane, a polyether polyester copolymer, polypropylene oxide,silicone, urethane, silicone-urethane copolymer, polycarbonate-urethanecopolymer, polyethylene terephthalate, saline, beta-glucan, hyaluronicacid and derivatives thereof, polyvinyl pyrrolidone or a hydrogelderivative thereof, dextrans or a hydrogel derivative thereof, glycerol,polyethylene glycol, Pluronic® type block copolymers (i.e., based onethylene oxide and propylene oxide), succinylated collagen, liquidcollagen, and other polysaccharides or biocompatible polymers orcombinations thereof.

In certain illustrative embodiments, the composition is porous.

In certain illustrative embodiments, the porous composition furthercomprises one or more bioactive agents, which slowly diffuse into thesurrounding tissue after implantation.

In certain illustrative embodiments, the one or more bioactive agentspromote growth or reduce inflammation.

In another embodiment, the invention encompasses a combination nucleuspulposus replacement and annulus fibrosus repair system comprising:

a. nucleus replacement composition comprising:

i. an outer surface comprised of a biocompatible material and adapted toconform to an inner wall of an annulus fibrosus and comprising a valveattached to the outer surface comprising a rigid socket geometry; and

ii. an inner surface having a central recess capable of receiving a loadbearing polymeric or elastomeric material,

wherein the outer and inner surfaces define a solid, deformablethickness therebetween; and

b. an annulus fibrosus plug comprising a ball fitting that connects withthe valve of the nucleus replacement composition, wherein the ballfitting comprises a plug of a natural or synthetic material thatpromotes cell in-growth with the surrounding annulus fibrosus.

In certain illustrative embodiments, the ball fitting of the annulusfibrosus plug can be formed of other shaped fittings, for example, anelliptical fitting.

In certain illustrative embodiments, the repair system further comprisesa guide for inserting and/or connecting the annulus fibrosus plug withthe nucleus replacement composition.

In certain illustrative embodiments, the rigid socket geometry iscomprised of a metal, plastic (e.g., polyether ether ketone) orcombination thereof.

In another embodiment, the invention encompasses a method of replacing anucleus pulposus comprising:

a. removing the nucleus pulposus through an opening in the annulusfibrosus to create a nucleus cavity;

b. inserting a nucleus pulposus replacement composition comprising afillable central cavity into the nucleus cavity;

c. filling elastomeric beads suspended in a biocompatible fluid or gelinto the nucleus pulposus replacement composition; and

d. plugging the annulus fibrosus.

In certain illustrative embodiments, the removing of the nucleuspulposus is done using forceps.

In certain illustrative embodiments, the inserting a nucleus pulposusreplacement composition is done using an endoscope or catheter.

In certain illustrative embodiments, the opening in the annulus isthrough a tear or injury in the annulus fibrosus.

In certain illustrative embodiments, the nucleus pulposus replacementcomposition is comprised of one or more biocompatible elastomerscomprised of thermoplastic polyurethane elastomer, polysiloxane modifiedstyrene-ethylene/butylene block copolymer, polycarbonate-urethane,polycarbonate-urethane cross-linked by a polyol, silicone rubber,silicone elastomer, polyether urethane, polyester urethane, a polyetherpolyester copolymer, polypropylene oxide, and combinations thereof.

In certain illustrative embodiments, the nucleus pulposus replacementcomposition is in the form of an inflatable balloon.

In certain illustrative embodiments, the inflatable balloon comprisesone or more lumen.

In certain illustrative embodiments, the elastomeric beads are comprisedof silicone, urethane, silicone-urethane copolymer,polycarbonate-urethane copolymer, polyethylene terephthalate, orcombinations thereof.

In certain illustrative embodiments, the biocompatible fluid or gel isbeta-glucan, hyaluronic acid and derivatives thereof, polyvinylpyrrolidone or a hydrogel derivative thereof, dextrans or a hydrogelderivative thereof, glycerol, polyethylene glycol, Pluronic® type blockcopolymers (i. e., based on ethylene oxide and propylene oxide),succinylated collagen, liquid collagen, and other polysaccharides orbiocompatible polymers or combinations thereof.

In certain embodiments, the plugging of annulus fibrosus comprisessutures (e.g., resorbable or non-resorbable strips/cords/drawstrings/wires/cords), scaffolds (e.g., fibrous weaved textiles),adhesives (e.g., fibrin, cyanoacrylates, polyanhydrides,glutaraldehydes, PRP), in-situ fabricated plugs (e.g., single sheetwound or two piece snapped together), pre-fabricated plugs, expandableplugs (e.g., stent like), or combinations thereof.

Nucleus Replacement Technology of the Invention

The invention generally encompasses nucleus pulposus replacementcompositions that can be implanted with minimally invasive surgicalprocedures. Due to the composition, make-up and mechanical properties(e.g., flexibility and compressibility), the nucleus pulposusreplacement compositions of the invention will result in less blood lossduring implantation, shorter post-operative recovery times, and shortersurgical operation time.

In one embodiment, the invention encompasses a nucleus pulposusreplacement composition including a solid, deformable, load-bearingmaterial (e.g., an elastomeric balloon) and a plurality of elastomericbeads suspended in a biocompatible fluid or gel.

The nucleus pulposus replacement composition is useful for treating orreplacing one or more herniated or degenerated discs. In an illustrativeembodiment, the nucleus pulposus replacement composition is used inminimally invasive endoscopic disectomy (e.g., lumbar disectomy) fortreating or replacing one or more herniated or degenerated discs. Thenucleus pulposus replacement composition can support the annulusfibrosus and maintain its structural and functional integrity. To repairan injury, the nucleus material leaking from the opening or tear in theannulus fibrosus is removed in a minimally invasive surgical operationto form a nucleus cavity. This may be carried out with, for example, aforceps-like instrument with which the jelly-like nucleus material iscut off and the opening may also be enlarged and its edges smoothed. Thenucleus pulposus replacement composition of the invention can then beinserted into the cavity as described herein.

In certain illustrative embodiments, the nucleus pulposus replacementcomposition incorporates a deflated deformable, load-bearing material(e.g., a single or multi-lumen elastomeric balloon), which can beinflated with an elastomeric material (e.g., elastomeric beads or balls)suspended in a biocompatible fluid or gel. The elastomeric materialsuspended in a biocompatible fluid or gel can be dispensed into thenucleus pulposus replacement composition using an endoscope or catheter.

In certain illustrative embodiments, the nucleus pulposus replacementcomposition can mimic the nucleus pulposus of a healthy subject and willbear physiologic loads through stiffness imparted by the elastomericbeads or balls and the hydrostatic pressure generated by thebiocompatible fluid or gel. The stiffness and internal hydrostaticpressure can assist load bearing, support the annulus fibrosus from allsides and prevent creep or effusion and stress relaxation of theelastomeric material. Motion can be achieved through the existingannulus and the deformation of the nucleus.

FIG. 1 illustrates a non-limiting, exemplary schematic of the insertion.In FIG. 1a , a deflated single- or multi-lumen balloon 110 can beinserted into the nucleus pulposus cavity 105 using a catheter orendoscope 130. FIG. 1b illustrates the inflating of the balloon usingmechanical or hydraulic means with load bearing microbeads 140 suspendedin biocompatible fluid or gel. FIG. 1c illustrates the plugging of theannular injury and removal of the catheter or endoscope.

FIGS. 1b and 1c also illustrate the inflated nucleus pulposusreplacement composition arranged between two vertebrae. Theintervertebral disc consists of the central nucleus and the annulusfibrosus surrounding it. It is understood that the upper vertebra restswith its lower end plate in a surface-to-surface manner in the same wayas the lower vertebra with its upper end plate against theintervertebral disc. FIG. 1c shows schematically how through an opening150 in the annulus fibrosus, for example, in the form of a tear, thenucleus pulposus replacement composition can be inserted.

The nucleus pulposus replacement composition comprising a solid,deformable, load-bearing material can be comprised of any durablematerial that is safe for in vivo transplantation including, but notlimited to, one or more biocompatible polymers of elastomers includingthermoplastic polyurethane elastomer, polysiloxane modifiedstyrene-ethylene/butylene block copolymer, polycarbonate-urethane,polycarbonate-urethane cross-linked by a polyol, silicone rubber,silicone elastomer, polyether urethane, polyester urethane, a polyetherpolyester copolymer, polypropylene oxide, and combinations thereof.

In certain illustrative embodiments, the plurality of elastomeric beadsor balls include any material that is safe for in vivo use including,but not limited to, silicone, urethane, silicone-urethane copolymer,polycarbonate-urethane copolymer, polyethylene terephthalate, orcombinations thereof.

In other illustrative embodiments, the biocompatible fluid or gelinclude any material that is safe for in vivo use including, but notlimited to, saline, beta-glucan, hyaluronic acid and derivativesthereof, polyvinyl pyrrolidone or a hydrogel derivative thereof,dextrans or a hydrogel derivative thereof, glycerol, polyethyleneglycol, succinylated collagen, liquid collagen, and otherpolysaccharides or biocompatible polymers or combinations thereof. Inother embodiments, the biocompatible fluid or gel. includes salts,alcohols, polyols, amino acids, sugars, proteins, polysaccharides,chondroitin sulfate, dermatan sulfate, heparin sulfate, biglycan,syndecan, keratocan, decorin, aggrecan, and combinations thereof.

FIG. 2a illustrates a non-limiting, exemplary blown up view of theinsertion of a deflated single- or multi-lumen balloon 110 into thenucleus pulposus cavity 105 using a catheter or endoscope 130, which isinserted through an injury or tear in the annulus fibrosus 120. FIG. 2billustrates the inflating of the balloon using mechanical or hydraulicmeans with load bearing microbeads 140 suspended in biocompatible fluidor gel 145. FIG. 2c illustrates the plugging of the annular injury 160and removal of the catheter or endoscope.

The invention also encompasses repairing an annular tear using, forexample, a resilient plug. Various materials can be utilized for thispurpose, including various polymers or elastomers.

Additionally, bioactive agents can be combined with the nucleuscompositions or annular material. “Bioactive agents,” as used herein,include, but are not limited to, chemotactic agents; therapeutic agents(e.g., antibiotics, steroidal and non-steroidal analgesics andanti-inflammatories (including certain amino acids such as glycine),anti-rejection agents such as immunosuppressants and anti-cancer drugs);various proteins (e.g., short term peptides, bone morphogenic proteins,collagen, hyaluronic acid, glycoproteins, and lipoprotein); cellattachment mediators; biologically active ligands; integrin bindingsequence; ligands; various growth and/or differentiation agents andfragments thereof (e.g., epidermal growth factor (EGF), hepatocytegrowth factor (HGF), vascular endothelial growth factors (VEGF),fibroblast growth factors (e.g., bFGF), platelet derived growth factors(PDGF), insulin derived growth factor (e.g., IGF-I, IGF-II) andtransforming growth factors (e.g., TGF-β I-II) parathyroid hormone,parathyroid hormone related peptide, bone morphogenic proteins (e.g.,BMP-2, BMP-4; BMP-6; BMP-7; BMP-12; BMP-13; BMP-14), sonic hedgehog,growth differentiation factors (e.g., GDF5, GDF6, GDF8), recombinanthuman growth factors (e.g., MP52, and MP-52 variant rhGDF-5),cartilage-derived morphogenic proteins (CDMP-1; CDMP-2, CDMP-3)); smallmolecules that affect the upregulation of specific growth factors;tenascin-C; hyaluronic acid; chondroitin sulfate; fibronectin; decorin;thromboelastin; thrombin-derived peptides; heparin-binding domains;heparin; heparan sulfate; DNA fragments and DNA plasmids; andcombinations thereof. Suitable effectors likewise include the agonistsand antagonists of the agents described above. The growth factor canalso include combinations of the growth factors described above. Inaddition, the growth factor can be autologous growth factor that issupplied by platelets in the blood. In this case, the growth factor fromplatelets will be an undefined cocktail of various growth factors. Ifother such substances have therapeutic value in the orthopedic field, itis anticipated that at least some of these substances will have use inthe present invention, and such substances should be included in themeaning of “bioactive agent” and “bioactive agents” unless expresslylimited otherwise. Illustrative examples of preferred bioactive agentsinclude culture media, bone morphogenic proteins, growth factors, growthdifferentiation factors, recombinant human growth factors,cartilage-derived morphogenic proteins, hydrogels, polymers,antibiotics, anti-inflammatory medications, immunosuppressivemediations, autologous, allogenic or xenologous cells such as stemcells, chondrocytes, fibroblast and proteins such as collagen andhyaluronic acid. Bioactive agents can be synthetic (e.g., bioactiveglass), autologus, allogenic, xenogenic or recombinant.

In another embodiment, the invention encompasses a nucleus pulposusimplant that can replace a herniated or degenerated nucleus disc. Incertain embodiments, the herniated or degenerated nucleus disc is in theearly stages of degenerative disc disease. In certain embodiments, theannulus fibrosus is kept intact and can maintain normal functionality.

In various embodiments, the nucleus pulposus implant is composed of apolymeric or elastomeric material that has the mechanical propertiesthat mimic the nucleus pulposus of a healthy subject including, but notlimited to, one or more biocompatible polymers of elastomers includingthermoplastic polyurethane elastomer, polysiloxane modifiedstyrene-ethylene/butylene block copolymer, polycarbonate-urethane,polycarbonate-urethane cross-linked by a polyol, silicone rubber,silicone elastomer, polyether urethane, polyester urethane, a polyetherpolyester copolymer, polypropylene oxide, and combinations thereof.

In certain embodiments, the nucleus pulposus implant is composed of apolymeric or elastomeric material that is compressible and flexible toallow insertion and implantation endoscopically without causing theimplant to substantially lose shape or form.

In other embodiments, the nucleus pulposus implant is composed of apolymeric or elastomeric material that is porous and accordinglybioactive agents as defined herein can be loaded into the implant, forexample, to promote growth or to alleviate pain associated withdegeneration.

In one embodiment, the nucleus implant composition comprises a singlebiocompatible polymeric or elastomeric material in the form of aplurality of concentric coils, wherein the outermost perimeter conformsto an inner wall of an annulus fibrosus.

FIG. 3 illustrates a non-limiting, nucleus implant composition comprisesa single biocompatible polymeric or elastomeric material in the form ofa plurality of concentric coils, for example, in the shape of a spring(e.g., spring nucleus replacement composition). A top view in FIG. 3blooks like concentric circles when it is compressed leaving no space orin certain embodiments small amounts of space between the coils of thespring.

In certain embodiments, the spring nucleus replacement composition hasthe ability to spiral up or spiral down. In various embodiments, thespring nucleus replacement composition has the same height as theintended disc height to be restored. One skilled in the art will alsoconsider the cross section of the spring nucleus replacement compositionsince contact surface area help with load/force distribution in thespine.

In certain embodiments, the outermost perimeter (i.e., the lateralsides, top and bottom surfaces) of the spring nucleus replacementcomposition can be rounded so that the spring nucleus replacementcomposition can fit firmly to the annulus fibrosus and vertebralendplate. In an illustrative embodiment, a cross section for the springnucleus replacement composition includes a rounded rectangular figurewith rounded ends as illustrated in FIG. 3b . Preferably, the outerdiameter of the coil should be in contact with the annulus fibrosus.

In other illustrative embodiments, to achieve a desired disc height themore than one spring nucleus replacement composition can be insertedinto the nucleus, for example, in layers.

In another embodiment, the nucleus implant composition comprises asingle biocompatible polymeric or elastomeric material in the form of apre-shaped balloon, wherein the biocompatible elastomeric or polymericsolid, deformable, and load-bearing material comprises a center cavityand one or more envelope cavities surrounding the center cavity.

In certain embodiments, the center cavity and one or more envelopecavities surrounding the center cavity can be independently filled witha plurality of elastomeric beads and/or a biocompatible fluid or gel.

In various embodiments, the nucleus implant is composed of a polymericor elastomeric material that has the mechanical properties that mimicthe nucleus pulposus of a healthy subject including, but not limited to,one or more biocompatible polymers of elastomers including thermoplasticpolyurethane elastomer, polysiloxane modified styrene-ethylene/butyleneblock copolymer, polycarbonate-urethane, polycarbonate-urethanecross-linked by a polyol, silicone rubber, silicone elastomer, polyetherurethane, polyester urethane, a polyether polyester copolymer,polypropylene oxide, and combinations thereof.

In certain illustrative embodiments, the plurality of elastomeric beadsor balls include any material that is safe for in vivo use including,but not limited to, silicone, urethane, silicone-urethane copolymer,polycarbonate-urethane copolymer, polyethylene terephthalate, orcombinations thereof.

In other illustrative embodiments, the biocompatible fluid or gelinclude any material that is safe for in vivo use including, but notlimited to, saline, beta-glucan, hyaluronic acid and derivativesthereof, polyvinyl pyrrolidone or a hydrogel derivative thereof,dextrans or a hydrogel derivative thereof, glycerol, polyethyleneglycol, succinylated collagen, liquid collagen, and otherpolysaccharides or biocompatible polymers or combinations thereof. Inother embodiments, the biocompatible fluid or gel. includes salts,alcohols, polyols, amino acids, sugars, proteins, polysaccharides,chondroitin sulfate, dermatan sulfate, heparin sulfate, biglycan,syndecan, keratocan, decorin, aggrecan, and combinations thereof.

FIG. 4a illustrates a non-limiting, exemplary pre-shaped balloon nucleusreplacement that can be created to conform to the intervertebral disclevels (e.g., L1-S1). In certain non-limiting, exemplary embodiments,FIG. 4b illustrates a multiple envelope system that allows filling theenvelope cavity space, the center cavity or both of them. In certainembodiments, the biocompatible materials that can be used to fill thecenter or the envelope cavity include beads or saline.

Another embodiment encompasses a nucleus replacement compositioncomprised of one or more biocompatible elastomeric or polymericmaterials in the shape of a plurality of string-like implants. Invarious embodiments, the nucleus implant is composed of a polymeric orelastomeric material that has the mechanical properties that mimic thenucleus pulposus of a healthy subject including, but not limited to, oneor more biocompatible polymers of elastomers including thermoplasticpolyurethane elastomer, polysiloxane modified styrene-ethylene/butyleneblock copolymer, polycarbonate-urethane, polycarbonate-urethanecross-linked by a polyol, silicone rubber, silicone elastomer, polyetherurethane, polyester urethane, a polyether polyester copolymer,polypropylene oxide, and combinations thereof.

FIG. 5a illustrates a non-limiting, exemplary thin string nucleusimplant design. The thin string can be implanted through a tear in theannulus fibrosus and in illustrative embodiments the string is largerthan the tear or fissures to prevent leakage. FIG. 5b illustrates ablown up view of a thin string.

In certain embodiments, the implant will include a plurality of thinstrings. In certain embodiments, the diameter of the strings is largerthan the fissures/tears and annulotomy in the annulus so that upon entryin the IVD to fill the nucleus so it does not exit or effuse. The stringcan be comprised of tiny microbeads made into a string form or acylindrical string form.

In an illustrative embodiment, the method of insertion of the implant itthrough a cannula. The string will then be injected into the nucleuscavity and then the string expands out into the nucleus cavity. Incertain embodiments, this eliminates the need for annular repair.

In another embodiment, the invention encompasses a nucleus pulposuscontainment shell comprising a containment jacket including a nucleuspulposus filler material that provides minimally invasive surgical portdelivery, includes a containment jacket of known geometry and mechanicalproperties, filler material that maintains known pressure and preventsfuture expulsion, and includes anchorage to the vertebral endplates.

One illustrative embodiment encompasses a nucleus pulposus containmentshell comprising:

a. an outer shell comprised of a biocompatible material;

b. an inner surface capable of being filled with a load bearingpolymeric or elastomeric material,

c. a unidirectional valve for filling the inner surface; and

d. a sealing crimp to prevent leakage of the load bearing polymeric orelastomeric material filling the inner surface.

wherein the outer shell has an cylindrical-like shape, wherein a topsurface and/or a bottom surface are textured to provide anchorage withvertebral endplates.

Another illustrative embodiment encompasses a nucleus pulposuscontainment shell comprising:

a. an outer shell comprised of a biocompatible material;

b. an inner surface capable of being filled with a load bearingpolymeric or elastomeric material,

c. a unidirectional valve for filling the inner surface; and

d. a sealing crimp to prevent leakage of the load bearing polymeric orelastomeric material filling the inner surface.

wherein the outer shell has an tubular ring-like shape, wherein a topsurface and/or a bottom surface are textured to provide anchorage withvertebral endplates.

In certain illustrative embodiments, the containment shell is comprisedof (1) metals (e.g., titanium or titanium alloys, alloys with cobalt andchromium, cobalt-chrome, stainless steel); (2) plastics (e.g.,ultra-high molecular weight polyethylene (UHMWPE),polymethylmethacrylate (PMMA), polytetrafluoroethylene (PTFE),polyetheretherketone (PEEK), nylon, polypropylene, and/orPMMA/polyhydroxy-ethylmethacrylate (PHEMA)); (3) ceramics (e.g.,alumina, beryllia, calcium phosphate, and/or zirconia, among others);(4) composites; and/or the like. In some embodiments, the containmentshell is a metal foil shell. In certain embodiments, the materials maybe partially or completely bio-resorbable as desired or appropriate.

In other illustrative embodiments, the containment shell can include apartially or totally textured surface to allow anchorage with thevertebral endplates. As used herein, textured, refers to any grooved orrough texture (e.g., a Velcro®-like texture) or porous features thatincreases the friction and anchorage with the vertebral endplates.

FIGS. 6a and 6b illustrate a non-limiting, exemplary nucleus pulposuscontainment shell including an outer shell having a cylindrical shapeand a textured top and bottom surface to provide anchorage withvertebral endplates. The implant can be filled with a load bearingpolymeric or elastomeric material filling to allow the implant toconform to the shape of the annulus fibrosus. The illustrative,non-limiting implant includes a metal foil shell or polymer shell (e.g.,urethanes, silicones), or a combination thereof, a unidirectional valvefor filling the inner surface; and a sealing crimp to prevent leakage ofthe load bearing polymeric or elastomeric material filling the innersurface.

FIGS. 7a-7c illustrates a second non-limiting, exemplary nucleuspulposus containment shell including an outer shell having a tubularring-like shape and a textured top and bottom surface to provideanchorage with vertebral endplates. The implant can be filled with aload bearing polymeric or elastomeric material filling to allow theimplant to conform to the shape of the annulus fibrosus. Theillustrative, non-limiting implant includes a metal foil shell, aunidirectional valve for filling the inner surface; and a sealing crimpto prevent leakage of the load bearing polymeric or elastomeric materialfilling the inner surface.

In certain embodiments, the load bearing polymeric or elastomericmaterial is a thermoplastic polyurethane elastomer, polysiloxanemodified styrene-ethylene/butylene block copolymer,polycarbonate-urethane, polycarbonate-urethane cross-linked by a polyol,silicone rubber, silicone elastomer, polyether urethane, polyesterurethane, a polyether polyester copolymer, polypropylene oxide,silicone, urethane, silicone-urethane copolymer, polycarbonate-urethanecopolymer, polyethylene terephthalate, saline, beta-glucan, hyaluronicacid and derivatives thereof, polyvinyl pyrrolidone or a hydrogelderivative thereof, dextrans or a hydrogel derivative thereof, glycerol,polyethylene glycol, succinylated collagen, liquid collagen, and otherpolysaccharides or biocompatible polymers or combinations thereof.

Generally, the nucleus containment shell includes a unidirectional valveto allow filling of the containment shell with the load bearingpolymeric or elastomeric material. In addition, the nucleus containmentshell includes a sealing crimp to prevent leakage of the load bearingpolymeric or elastomeric material.

In another embodiment, the invention encompasses a combination nucleuspulposus replacement and annulus fibrosus repair system comprising:

a. nucleus replacement composition comprising:

-   -   i. an outer surface comprised of a biocompatible material and        adapted to conform to an inner wall of an annulus fibrosus and        comprising a valve attached to the outer surface comprising a        rigid socket geometry; and    -   ii. an inner surface having a central recess capable of        receiving a load bearing polymeric or elastomeric material,

wherein the outer and inner surfaces define a solid, deformablethickness therebetween; and

b. an annulus fibrosus plug comprising a ball fitting (or other shapedfitting) that connects with the valve of the nucleus replacementcomposition, wherein the ball fitting (or other shaped fitting)comprises a plug of a natural or synthetic material that promotes cellin-growth (e.g., a fibrous or woven structure that includes a cellgrowth media) with the surrounding annulus fibrosus.

In certain embodiments, the repair system includes a guide for insertingand/or connecting the annulus fibrosus plug with the nucleus replacementcomposition. In certain embodiments, the rigid socket geometry iscomprised of a metal, a plastic (e.g., polyether ether ketone) or acombination thereof.

In certain embodiments, the valve attached to the outer surfacecomprises a rigid socket geometry (i.e., a female part) that can matewith a rigid ball (or other shape, for example, elliptical) geometry ofthe annulus plug (i.e., a male part).

The nucleus pulposus replacement composition can be comprised of anydurable material that is safe for in vivo transplantation including, butnot limited to, one or more biocompatible polymers of elastomersincluding thermoplastic polyurethane elastomer, polysiloxane modifiedstyrene-ethylene/butylene block copolymer, polycarbonate-urethane,polycarbonate-urethane cross-linked by a polyol, silicone rubber,silicone elastomer, polyether urethane, polyester urethane, a polyetherpolyester copolymer, polypropylene oxide, and combinations thereof.

In certain illustrative embodiments, the load bearing polymeric orelastomeric material includes a plurality of elastomeric beads or ballssuspended in a biocompatible fluid or gel.

In certain illustrative embodiments, the plurality of elastomeric beadsor balls include any material that is safe for in vivo use including,but not limited to, silicone, urethane, silicone-urethane copolymer,polycarbonate-urethane copolymer, polyethylene terephthalate, orcombinations thereof.

In other illustrative embodiments, the biocompatible fluid or gelinclude any material that is safe for in vivo use including, but notlimited to, saline, beta-glucan, hyaluronic acid and derivativesthereof, polyvinyl pyrrolidone or a hydrogel derivative thereof,dextrans or a hydrogel derivative thereof, glycerol, polyethyleneglycol, Pluronic® type block copolymers (i.e., based on ethylene oxideand propylene oxide), succinylated collagen, liquid collagen, and otherpolysaccharides or biocompatible polymers or combinations thereof. Inother embodiments, the biocompatible fluid or gel. includes salts,alcohols, polyols, amino acids, sugars, proteins, polysaccharides,chondroitin sulfate, dermatan sulfate, heparin sulfate, biglycan,syndecan, keratocan, decorin, aggrecan, and combinations thereof. Inother embodiments, the fluid or gel includes in situ curable materials,for example, polyurethanes and silicones) that will form a solid insitu.

In certain illustrative embodiments, the annulus fibrosus plug isattached to a ball fitting (or other shaped fitting) that allowsconnection with the nucleus replacement composition. FIG. 11 illustratesa schematic of insertion of the annulus plug into the nucleusreplacement composition using a removable guide. In certain embodiments,the annulus plug material can be comprised of a weave of fibers or asponge (i.e., a natural or synthetic material) as illustrated in FIG.10a to make a porous plug that permits or promotes in vivo cellin-growth from the surrounding annulus and accordingly can include abioactive agent.

FIGS. 12a and 12b illustrate a non-limiting, exemplary embodiment of anucleus pulposus implant including a check valve just prior toattachment of annulus fibrosus plug. The annulus fibrosus plug isattached to a guide and being inserted into the annulus fibrosus tear.

Kits

The invention also contemplates kits including a nucleus replacementcomposition and an annulus fibrosus plug and the equipment and materialsrequired to insert the composition into the intervertebral cavity. FIG.10b illustrates annulus fibrosus plugs of varying sizes that can be cutby a surgeon to seal a tear or cut in the subject's annulus fibrosus.

Accordingly, the nucleus replacement composition and an annulus fibrosuscan be manufactured in varying widths, lengths, and dimensions toaccommodate the type of surgery and needs of the surgeon.

In addition, the kits can also include the load bearing polymeric orelastomeric material including a plurality of elastomeric beads or ballssuspended in a biocompatible fluid or gel and the necessary cannulas toadminister them.

The kits of the invention are intended to broaden a surgeon's optionsonce in surgery to provide a patient with the most optimal nucleusreplacement composition and annulus fibrosus repair technology.

EXAMPLES Example 1

To repair a herniated disk injury, nucleus material leaking from anopening in the annulus fibrosus is removed in a surgical operation toform a nucleus cavity. This may be carried out with, for example, aforceps-like instrument with which the jelly-like nucleus material iscut off and the opening may also be enlarged and its edges smoothed. Thethus removed nucleus material may be used for growing a culture of thepatient's own body cells.

A nucleus pulposus replacement composition is then inserted through theopening in the annulus and into the nucleus cavity. The nucleus pulposusreplacement composition includes, for example, a biocompatible solid,deformable, load-bearing material in the form of a balloon, which isdeflated and incorporated into the nucleus cavity using a catheter andis selected in relation to the size of the opening such that uponintroducing the nucleus pulposus replacement composition into theopening, the opening is not unnecessarily enlarged. The nucleus pulposusreplacement composition may have, for example, the shape of a relativelynarrow rectangular parallelepiped. The nucleus pulposus replacementcomposition is connectable by a rod to a handle which can be removed,for example, by unscrewing.

After insertion of the nucleus pulposus replacement composition, thecomposition can be filled with, for example, a plurality of elastomericbeads suspended in a biocompatible fluid or gel. The amount of beads andgel can be determined by the surgeon during surgery and depends on thepatient's physiology, the location on the vertebra of the implant, andother mechanical and physical properties apparent to the surgeon.

The annulus fibrosus plug comprising a ball fitting (or other shapedfitting) is then inserted into the tear or incision in the annulus ofthe patient. The annulus fibrosus plug connects with a check valve ofthe nucleus replacement composition, wherein a ball fitting comprises aplug of a natural or synthetic material that promotes cell in-growth(e.g., a fibrous or woven structure that includes a cell growth media)with the surrounding annulus fibrosus.

The annulus fibrosus plug is pushed into the opening using a suitableinsertion instrument, which releasably grips the implant. Once theannulus fibrosus plug has been pushed fully into the opening, theinsertion instrument may be released and removed. As will be apparent,the annulus fibrosus plug now closes the opening in the patient'sannulus and is supported at its upper face on the end plate of an uppervertebra and at its lower face on the end plate of a lower vertebra.

In various embodiments, the annulus fibrosus plug comprises of aresorbable material and is porous. The size of the pores is betweenabout 50 μm and about 500 μm. The material of the plug-shaped implant isflexible and elastic, so that it adapts optimally to the contour of theopening and also easily follows the movements of the material of theannulus fibrosus. The nucleus pulposus replacement is less deformable orelastic in the same way as the rest of the material of the implant. Thisresults in a rigid connection in the area in which the implant is fixedto the adjacent vertebrae. The material of the implant adapts to themovability of the material of the annulus fibrosus and reliably closesthe opening.

In this way, the entire material of the plug may be flexible or elastic,but it is also possible for the material of the plug to becomeprogressively firmer. When the opening in the annulus fibrosus has beenclosed in this way, cell material grown outside of the body (e.g., in aculture) can be introduced into the interior of the intervertebral disc.For example, this is carried out approximately weeks after the surgicaloperation described above. Alternatively, the porous annulus fibrosuscan be coated with a bioactive agent that promotes cell growth orprovides a therapeutic effect.

In the specification, there have been disclosed typical preferredembodiments of the invention and, although specific terms are employed,they are used in a generic and descriptive sense only and not forpurposes of limitation. Obviously many modifications and variations ofthe invention are possible in light of the above teachings. It istherefore to be understood that the invention may be practiced otherwisethan as specifically described.

Unless defined otherwise, all technical and scientific terms and anyacronyms used herein have the same meanings as commonly understood byone of ordinary skill in the art in the field of this invention.Although any compositions, methods, kits, and means for communicatinginformation similar or equivalent to those described herein can be usedto practice this invention, the preferred compositions, methods, kits,and means for communicating information are described herein.

All references cited above are incorporated herein by reference to theextent allowed by law. The discussion of those references is intendedmerely to summarize the assertions made by their authors. No admissionis made that any reference (or a portion of any reference) is relevantprior art. Applicants reserve the right to challenge the accuracy andpertinence of any cited reference.

What is claimed is:
 1. A method of surgery comprising: removing at leasta portion of a nucleus pulposus through an annulus fibrosus to create acavity; inserting a nucleus pulposus replacement device in the cavity,wherein the device comprises: an outer shell comprised of abiocompatible material defining a central fillable cavity having acentral cavity and one or more envelope cavities completely surroundingan outer perimeter of the central cavity; an inner surface capable ofreceiving a load bearing polymeric or elastomeric material; a valve toallow filling of the inner surface; and a sealing crimp.
 2. The methodof surgery of claim 1, wherein the nucleus pulposus replacement deviceis inserted with an endoscope.
 3. The method of surgery of claim 1,wherein the outer shell is comprised of a metallic material.
 4. Themethod of surgery of claim 3, wherein the metallic material comprisesNiTi alloy, stainless steel, titanium, or combinations thereof.
 5. Themethod of surgery of claim 1, wherein the outer shell is comprised of apolymeric material.
 6. The method of surgery of claim 1, furthercomprising filling the inner surface with the load bear polymeric orelastomeric material, wherein the load bearing polymeric or elastomericmaterial includes a plurality of elastomeric beads or balls suspended ina biocompatible fluid or gel.
 7. The method of claim 6, wherein theplurality of elastomeric beads or balls comprises silicone, urethane,silicone-urethane copolymer, polycarbonate-urethane copolymer,polyethylene terephthalate, or combinations thereof.
 8. The method ofclaim 1, wherein the valve comprises a unidirectional valve.
 9. Themethod of claim 1, wherein the nucleus pulposus replacement device iscylindrically shaped.
 10. The method of claim 1, wherein the nucleuspulposus replacement device includes a textured top surface and atextured bottom surface.
 11. A method of surgery comprising: removing atleast a portion of a nucleus pulposus through an annulus fibrosus tocreate a cavity; inserting a nucleus pulposus replacement device in thecavity, wherein the device comprises: an outer shell having a topsurface, a bottom surface, and lateral sides comprised of abiocompatible material; an inner surface capable of receiving a loadbearing polymeric or elastomeric material; a valve to allow filling ofthe inner surface; and a sealing crimp, wherein the outer shell has atubular ring-like shape, and wherein, when inflated with the loadbearing polymeric or elastomeric material, the top and bottom surfacesand lateral sides of the tubular ring are rounded so that the nucleuspulposus containment shell is configured to fit firmly to the annulusfibrosus and vertebral endplates.
 12. The method of claim 11, whereininserting the nucleus pulposus replacement device is performed using anendoscope.
 13. The method of surgery of claim 11, wherein the outershell is comprised of a metallic material.
 14. The method of surgery ofclaim 13, wherein the metallic material comprises NiTi alloy, stainlesssteel, titanium, or combinations thereof.
 15. The method of surgery ofclaim 11, wherein the outer shell is comprised of a polymeric material.16. The method of surgery of claim 11, further comprising filling theinner surface with the load bear polymeric or elastomeric material,wherein the load bearing polymeric or elastomeric material includes aplurality of elastomeric beads or balls suspended in a biocompatiblefluid or gel.
 17. The method of claim 16, wherein the plurality ofelastomeric beads or balls comprises silicone, urethane,silicone-urethane copolymer, polycarbonate-urethane copolymer,polyethylene terephthalate, or combinations thereof.
 18. The method ofclaim 11, wherein the valve comprises a unidirectional valve.
 19. Themethod of claim 11, wherein the nucleus pulposus replacement device iscylindrically shaped.
 20. The method of claim 11, wherein the nucleuspulposus replacement device includes a textured top surface and atextured bottom surface.